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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents

ID: 428380.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Effects of cell-penetrating peptides and pegylation on transfection efficiency of polyethylenimine in mouse lungs
Authors:Nguyen, J.; Xie, X.; Neu, M.; Dumitrascu, R.; Reul, R.; Sitterberg, J.; Bakowsky, U.; Schermuly, R.; Fink, L.; Schmehl, T.; Gessler, T.; Seeger, W.; Kissel, T.
Date of Publication (YYYY-MM-DD):2008
Title of Journal:J Gene Med
Issue / Number:11
Start Page:1236
End Page:1246
Audience:Not Specified
Abstract / Description:BACKGROUND: Cell-penetrating peptides (CPPs) could potentially be used as vectors for intracellular delivery of proteins, peptides and nucleic acids. The present study examined different CPPs, such as TAT-derived and arginine rich sequences, as well as model amphiphilic peptide, with respect to transfection efficiency of pegylated polyethylenimine (PEI) in A549, Calu-3 cells and in mice after intra-tracheal administration. METHODS: The conjugates were prepared by the coupling of CPPs to PEI via a heterobifunctional polyethylene glycol (PEG) linker, resulting in the bioconjugates CPP-PEG-PEI. Structures were successfully confirmed by (1)H-nuclear magnetic resonance and diffusion-ordered spectroscopy. Unmodified PEI 25 kDa was compared with pegylated PEI, and aggregation tendency in cell culture medium, interaction with mucin and stability against heparin was assayed. After evaluating transfection efficiency of the polymers in two different lung cell lines, luciferase reporter gene expression was determined in mouse lungs. RESULTS: All conjugates showed superior transfection efficiency compared to unmodified PEI 25 kDa. The conjugates sizes were generally < 300 nm, thus enabling them to penetrate through the mucus lining of the lung and reach the target cells. Coupling of CPPs to PEG-PEI, however, did not significantly improve transfection efficiency in A549 cells, calu-3 cells and in mouse lungs. CONCLUSIONS: We show that small and stable polyplex size achieved by pegylation is favourable for successful pulmonary gene delivery. Compared to PEI 25 kDa, pegylated PEI and CPP-PEG-PEI displayed enhanced transfection efficiency both in vitro and in vivo.
Free Keywords:Amino Acid Sequence Animals Cells, Cultured Gene Transfer Techniques Genetic Vectors/administration & dosage Lung/*metabolism Magnetic Resonance Spectroscopy Mice Microscopy, Atomic Force Molecular Sequence Data Peptides/administration & dosage/*chemistry Polyethylene Glycols/*chemistry Polyethyleneimine/administration & dosage/*chemistry *Transfection
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
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